One of the major questions of tumor biology is why the cell- mediated host defense does not remove tumors carrying "foreign" antigens? One possible answer is the findings of several investigators that the serum of human animals have antibody-like factors which block lymphocyte killing of tumor cells. The presence of these blocking factors is directly related to progressive growth of the neoplasm. The work proposed here is to examine a model of lymphocyte, antigen and antibody interaction, and how antibody can influence the lymphocyte response. The major parts of the model consist of lymphocytes, mitogens (Con A and PHA), and antibody to each of these mitogens. Preliminary investigations have shown that antibody to the mitogens supresses the lymphocytes response by either 1) interfering with mitogen interaction with the lymphocyte or 2) by blocking lymphocyte reaction after the mitogens have bound to the responsive cells. The antibody does not remove the mitogen from the lymphocytes, but in some way alters the cell's responsiveness. This antibody induced suppression of lymphocyte bound mitogen will be used to determine possible mechanisms of central regulation of lymphocyte reactions. The suppressive behavior of different classes of immunoglobulin, the ability of antibody to suppress B and T lymphocytes, and the point in the metabolism of a stimulated cell suppressed by antibody will be determined. Using fluorescent probes and cell surface labeling studies, the influence of antibody on the mitogen induced changes in the cell surface will be examined. Other experiments will explore the ability of antibody to suppress lymphocyte cytotoxicity and mediator production, and determine the mechanism of antibody suppression when lymphocytes are stimulated with mitogens of various forms. Also, attempts will be made to overcome the suppressive state, and induce an augmented reaction to the stimulus. These studies will give a greater insight into how antibody can regulate the lymphocyte response to tumor antigens.